Although fatigue has the greatest impact on quality of life in people with MS, few studies have rigorously investigated the impact of DMTs on fatigue. Comparisons between study outcomes using different PRO tools is challenging due to the variety of psychometric constructs addressed by the questionnaires and differences in the recall period for fatigue symptoms and the measurement scale. Furthermore most of the PRO tools used to quantify MS-fatigue in studies of DMTs are descended from PRO tools developed during the 1990s before DMTs emerged and before widespread patient involvement in PRO development. New PRO tools should involve patients in their development as recommended by the US Food and Drug Administration and the validation process should consider the sensitivity of the PRO tool to change in fatigue over time or between groups.